US3072637A - delta4-pregnene-20-imino derivatives and process for their preparation - Google Patents
delta4-pregnene-20-imino derivatives and process for their preparation Download PDFInfo
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- US3072637A US3072637A US860674A US86067459A US3072637A US 3072637 A US3072637 A US 3072637A US 860674 A US860674 A US 860674A US 86067459 A US86067459 A US 86067459A US 3072637 A US3072637 A US 3072637A
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- pregnene
- imino
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- pregnane
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- 238000000034 method Methods 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title description 2
- -1 20-KETO-PREGNANE COMPOUND Chemical class 0.000 claims description 8
- 238000000197 pyrolysis Methods 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 5
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 229910052987 metal hydride Inorganic materials 0.000 claims description 3
- 150000004681 metal hydrides Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 150000003141 primary amines Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229960003387 progesterone Drugs 0.000 description 4
- 239000000186 progesterone Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- RSRDWHPVTMQUGZ-OZIWPBGVSA-N 1-[(8r,9s,10s,13s,14s,17s)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]ethanone Chemical class C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RSRDWHPVTMQUGZ-OZIWPBGVSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- VZRAKVPDZIQRGT-WZBAXQLOSA-N (8r,9s,10s,13r,14s,17r)-17-ethenyl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C=C)[C@@H]4[C@@H]3CCC21 VZRAKVPDZIQRGT-WZBAXQLOSA-N 0.000 description 1
- AURFZBICLPNKBZ-JMTGGFPBSA-N 1-[(3r,8r,9s,10s,13s,14s,17s)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]ethanone Chemical compound C1CC2C[C@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 AURFZBICLPNKBZ-JMTGGFPBSA-N 0.000 description 1
- GPGPPYIWYMEUGA-SRJHXTLLSA-N 1-[(8r,9s,10s,13s,14s,17s)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]ethanamine Chemical group C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(N)C)[C@@]1(C)CC2 GPGPPYIWYMEUGA-SRJHXTLLSA-N 0.000 description 1
- YTSNYCZPBJTZBN-OZIWPBGVSA-N 1-[(8r,9s,10s,13s,14s,17s)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]ethanimine Chemical class C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=N)C)[C@@]1(C)CC2 YTSNYCZPBJTZBN-OZIWPBGVSA-N 0.000 description 1
- BFZHCUBIASXHPK-ODYOLWGQSA-N 11a-Hydroxyprogesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC(C(=O)C)[C@@]1(C)C[C@H]2O BFZHCUBIASXHPK-ODYOLWGQSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- WRYNUJYAXVDTCB-UHFFFAOYSA-M acetyloxymercury Chemical compound CC(=O)O[Hg] WRYNUJYAXVDTCB-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960002899 hydroxyprogesterone Drugs 0.000 description 1
- CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- GEOVEUCEIQCBKH-UHFFFAOYSA-N hypoiodous acid Chemical compound IO GEOVEUCEIQCBKH-UHFFFAOYSA-N 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- VVNXEADCOVSAER-UHFFFAOYSA-N lithium sodium Chemical compound [Li].[Na] VVNXEADCOVSAER-UHFFFAOYSA-N 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000003544 oxime group Chemical group 0.000 description 1
- 150000003128 pregnanes Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0036—Nitrogen-containing hetero ring
- C07J71/0042—Nitrogen only
Definitions
- the invention is based on the observation that 18:20- imino-pregnane compounds can be obtained in a simple manner when ZO-keto-pregnane and -allopregnane compounds are reacted with an aliphatic primary amine, the ZO-imino compounds formed reduced to the 20-amino compounds and the latter in the form of the N-halogen compounds, subjected to pyrolysis.
- the process is illustrated in the following scheme of partial formulae :UM j :l
- R indicates an aliphatic hydrocarbon radical, for example a methyl group, and Hal a halogen atom, especially chlorine.
- the ZO-ketO-pregnane compounds are reacted with aliphatic primary amines, for example methylamine, in the presence of strong inorganic or organic bases.
- Suitable bases are, for example, alkali metal or alkaline earth metal alcoholates or hydroxides, especially sodium methylate, and also quaternary ammonium bases, for example benzyl-trimethyl-ammonium hydroxide.
- the reaction is advantageously carried out in a suitable solvent, for example in alcohols, or in excess of amine, and at elevated temperature under pressure.
- nascent hydrogen is primarily suitable, as formed, for example, from alkali metals or alkaline earth metals and alcohols, for example sodium and ethanol.
- This reduction can also be carried out by means of metal hydrides, for example sodium-boron hydride or lithium-aluminurn hydride.
- the secondary 20-amino-pregnane compounds produced from the imines are converted into the corresponding ZO-halogen-amino compounds.
- This conversion takes place by reaction with hypohalous acids, such as hypochlorous, hypobromous or hypoiodous acid, as obtained from chlorine, bromine or iodine and an alkali metal hydroxide, or from N-halogen-amides or -imides, for example N-chlor-, N-bromor N-iodirnide or -amide.
- the N-halogen amino-pregnane compounds split 01f hydrogen halide with formation of the corresponding 18:20-imino-pregnane compounds.
- the pyrolysis is advantageously carried out with exclusion of air in a diluent, such as a high boiling hydrocarbon, for example mineral oil.
- a diluent such as a high boiling hydrocarbon, for example mineral oil.
- the process can, however, be conducted without diluent, for example by heating under high vacuum.
- the temperature required for the pyrolysis is above 250 C. for example between 300 and 350 C.
- the ZO-keto-pregnanes and -allopregnanes employed as starting materials for the present process can contain further substituents, such as e.g. free, esterified or etherified hydroxyl groups or ketalized, or enolized 0x0 groups or oxime-, hydrazoneor semicarbazoneor alkyl groups, for example methyl groups.
- substituents are present, for example, in the positions 2, 3, 4, 9, 11, 12, 16. 0x0 groups in others than the 20-position must generally be protected prior to amination.
- ll-ketones can also be present in the free form.
- the starting materials can also possess double bonds in the ring system, for example in one or more of the positions 1, 4, 5, 9 (11), 11.
- compounnds useful as starting materials there may be especially mentioned: 3 8-hydroxy-20-oxo-allopregnane, 3a-hydroxy-ZO-oxo-pregnane, A -3B-hydroxy- 20-oxo-pregnene, progesterone, 11a-hydroxy-progesterone,1l-oxo-progesterone, and also 3- or ll-esters or 3- ketals, for example 3-ethylene ketals or the said compounds.
- the ZO-imino-pregnane compounds with an aliphatic hydrocarbon radical on the nitrogen atom, formed as intermediate products, are new.
- a -18:ZO-imino-pregnenes may be obtained by treating an 18:20-imino-pregnane compound with a halogenating agent, for example, chlorosnccinimide, and treating the N-halogeno-compound formed with a base, such as an hydroxide or alcoholate of an alkali or alkaline earth metal; or by introducing the 20zN-double bond by direct dehydrogenation, for example, by means of mercury acetate.
- 18-oxygenated pregnane compounds are obtained in a simple manner by treating the desired A -18:ZO-iminO-pregnene with nitrous acid and subsequently with an oxidizing agent.
- Example 5 grams of A -3 3-acetoxy-ZO-oxo-pregnene are heated for 7 hours in a closed tube with a solution of 5 grams of methylamine in 25 cc. of absolute methanol and 25 cc. of sodium methylate, prepared by dissolving 1.5 grams of sodium in 25 cc. of methanol, to a temperature of 100 C. After working up, 4.1 grams of basic product are obtained which, in the crude state, melts at 221-222 C.
- This product is A -3 S-acetoxy-2O-methylimino-pregnene and without further purification it is dissolved in cc. of absolute ethanol and reduced at boiling temperature by addition of 4 grams of sodium. By this means, in practically quantitative yield (3.5 grams) the A -3 8-hydroxy-20-methylamino-pregnene is produced. It is also obtainable starting from the above irriine by reduction with sodium-boron hydride in absolute methanol or lithium-aluminum hydride in absolute tetrahydrofuran.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
United States Patent 3,072,637 M-PREGNENE-ZO-IMINO DERIVATIVES AND PROCESS FOR THEIR PREPARATION Oskar Jeger, Zurich, Switzerland, assignor to Ciba Corporation, a corporation of Delaware No Drawing. Filed Dec. 21, 1959, Ser. No. 860,674 Claims priority, application Switzerland Jan. 16, 1959 13 Claims. (Cl. 260-2395) The invention is based on the observation that 18:20- imino-pregnane compounds can be obtained in a simple manner when ZO-keto-pregnane and -allopregnane compounds are reacted with an aliphatic primary amine, the ZO-imino compounds formed reduced to the 20-amino compounds and the latter in the form of the N-halogen compounds, subjected to pyrolysis. The process is illustrated in the following scheme of partial formulae :UM j :l
In these formulae R indicates an aliphatic hydrocarbon radical, for example a methyl group, and Hal a halogen atom, especially chlorine.
In carrying out the process the ZO-ketO-pregnane compounds are reacted with aliphatic primary amines, for example methylamine, in the presence of strong inorganic or organic bases. Suitable bases are, for example, alkali metal or alkaline earth metal alcoholates or hydroxides, especially sodium methylate, and also quaternary ammonium bases, for example benzyl-trimethyl-ammonium hydroxide. The reaction is advantageously carried out in a suitable solvent, for example in alcohols, or in excess of amine, and at elevated temperature under pressure.
For the reduction of the resulting 20-imino compounds nascent hydrogen is primarily suitable, as formed, for example, from alkali metals or alkaline earth metals and alcohols, for example sodium and ethanol. This reduction can also be carried out by means of metal hydrides, for example sodium-boron hydride or lithium-aluminurn hydride.
The secondary 20-amino-pregnane compounds produced from the imines are converted into the corresponding ZO-halogen-amino compounds. This conversion takes place by reaction with hypohalous acids, such as hypochlorous, hypobromous or hypoiodous acid, as obtained from chlorine, bromine or iodine and an alkali metal hydroxide, or from N-halogen-amides or -imides, for example N-chlor-, N-bromor N-iodirnide or -amide.
On heating, the N-halogen amino-pregnane compounds split 01f hydrogen halide with formation of the corresponding 18:20-imino-pregnane compounds. The pyrolysis is advantageously carried out with exclusion of air in a diluent, such as a high boiling hydrocarbon, for example mineral oil. The process can, however, be conducted without diluent, for example by heating under high vacuum. The temperature required for the pyrolysis is above 250 C. for example between 300 and 350 C.
ice
The ZO-keto-pregnanes and -allopregnanes employed as starting materials for the present process can contain further substituents, such as e.g. free, esterified or etherified hydroxyl groups or ketalized, or enolized 0x0 groups or oxime-, hydrazoneor semicarbazoneor alkyl groups, for example methyl groups. These substituents are present, for example, in the positions 2, 3, 4, 9, 11, 12, 16. 0x0 groups in others than the 20-position must generally be protected prior to amination. However, ll-ketones can also be present in the free form. The starting materials can also possess double bonds in the ring system, for example in one or more of the positions 1, 4, 5, 9 (11), 11.
Among compounnds useful as starting materials there may be especially mentioned: 3 8-hydroxy-20-oxo-allopregnane, 3a-hydroxy-ZO-oxo-pregnane, A -3B-hydroxy- 20-oxo-pregnene, progesterone, 11a-hydroxy-progesterone,1l-oxo-progesterone, and also 3- or ll-esters or 3- ketals, for example 3-ethylene ketals or the said compounds. l
The ZO-imino-pregnane compounds with an aliphatic hydrocarbon radical on the nitrogen atom, formed as intermediate products, are new. There may be especially mentioned the 20-methyl-imino compounds of 3,13-hydroxy-20-oxo-allopregnane, 3a-hydroxy-20-oxo-pregnane, A -3fi-hydroxy-20-oxo-pregnene, progesterone, 11u-hydroxy-progesterone, ll-oxo-progesterone, and also their 3- or ll-esters or S-ketals.
The 18:20-imino-pregnane compounds obtained as final products can be converted by the process of patent application Serial No. 859,576, filed December 15,1959, into 1-8-oxygenated 20-oxo-pregnanes. As is shown in this application, A -18:ZO-imino-pregnenes may be obtained by treating an 18:20-imino-pregnane compound with a halogenating agent, for example, chlorosnccinimide, and treating the N-halogeno-compound formed with a base, such as an hydroxide or alcoholate of an alkali or alkaline earth metal; or by introducing the 20zN-double bond by direct dehydrogenation, for example, by means of mercury acetate. 18-oxygenated pregnane compounds are obtained in a simple manner by treating the desired A -18:ZO-iminO-pregnene with nitrous acid and subsequently with an oxidizing agent.
The following example illustrates the invention:
Example 5 grams of A -3 3-acetoxy-ZO-oxo-pregnene are heated for 7 hours in a closed tube with a solution of 5 grams of methylamine in 25 cc. of absolute methanol and 25 cc. of sodium methylate, prepared by dissolving 1.5 grams of sodium in 25 cc. of methanol, to a temperature of 100 C. After working up, 4.1 grams of basic product are obtained which, in the crude state, melts at 221-222 C.
This product is A -3 S-acetoxy-2O-methylimino-pregnene and without further purification it is dissolved in cc. of absolute ethanol and reduced at boiling temperature by addition of 4 grams of sodium. By this means, in practically quantitative yield (3.5 grams) the A -3 8-hydroxy-20-methylamino-pregnene is produced. It is also obtainable starting from the above irriine by reduction with sodium-boron hydride in absolute methanol or lithium-aluminum hydride in absolute tetrahydrofuran.
For conversion into A -N-chloro-2Oa-N-methylamino- 3 fl-hydroxy-pregnene 1 gram of A -3B-hydroxy-20-methylamino-pregnene is dissolved in 100 cc. of absolute ether and chlorinated by means of N-chloro-succinimide. Especially good yields of the desired N-chloro compound are obtained by working with freshly purified and finely powdered chlorination reagent and accurately measuring out the quantity used 1.05 mols).
For ring closure, which leads to A -3fi-hydroxy-l8z20- methylimino-pregnene, 1 gram of M-N-chloro-ZOa-N- methylamino-3p-hydroxy-pregnene is suspended in 100 cc. of mineral oil and the suspension heated with exclusion of air for 30 minutes to 330-350 C. The pyrolysis can also be carried out without diluent but in that case it is preferable to work under high vacuum.
In an analogous manner other 20-oXo-pregnane compounds, for example progesterone-3-monoethylene ketal and 11-oxo-progesterone-S-monoethylene ketal, can be converted into the corresponding 18:20 methylimino compounds.
What is claimed is:
1. Process for the manufacture of imino-steroid compounds, wherein a ZO-keto-pregnane compound is reacted with an aliphatic primary amine, the 20-imino compound formed is reduced to the ZO-amino compound with a reducing reagent selected from the group consisting of nascent hydrogen and metal hydrides, and the latter in the form of an N-halogen compound subjected to pyrolysis at a temperature of above 250 C.
2. Process as claimed in claim 1, wherein a 20-ketopregnane compound is reacted with methylamine, in the presence of a strong base.
3. Process as claimed in claim 2, wherein a ZO-ketopregnane compound is reacted with methylamine, in the presence of a light metal alcoholate.
4. Process as claimed in claim 1, wherein the resulting 20-imino-pregnane compounds are reduced to the corresponding 20-amino compounds by means of an alkali metal in the presence of an alcohol.
5. Process as claimed in claim 1, wherein the 20-halogen-amino compounds are subjected to pyrolysis by heating to 300350 C.
6. Process as claimed in claim 1, wherein A -3/8-acetoxy-ZO-oxo-pregnene is used as starting material.
pregnene.
13. A compound of the formula i G=NCH;
KAI- [Tb in which R represents a member selected from the group consisting of References Cited in the file of this patent UNITED STATES PATENTS 2,582,258 Julian Ian. 15, 1952 2,731,461 Ruschig et al Jan. 17, 1956 FOREIGN PATENTS 491,798 Great Britain Sept. 8, 1938
Claims (2)
1. PROCESS FOR THE MANUFACTURE OF IMINO-STEROID COMPOUNDS, WHEREIN A 20-KETO-PREGNANE COMPOUND IS REACTED WITH ANALIPHATIC PRIMARY AMINE, THE 20-IMINO COMPOUND FORMED IS REDUCED TO THE 20-AMINO COMPOUND WITH A REDUCING REAGENT SELECTED FROM THE GROUP CONSISTING OF NASCENT HYDROGEN AND METAL HYDRIDES, AND THE LATTER IN THE FORM OF AN N-HALOGEN COMPOUND SUBJECTED TO PYROLYSIS AT A TEMPERATURE OF ABOVE 250* C.
13. A COMPOUND OF THE FORMULA
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH3072637X | 1959-01-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3072637A true US3072637A (en) | 1963-01-08 |
Family
ID=4573892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US860674A Expired - Lifetime US3072637A (en) | 1959-01-16 | 1959-12-21 | delta4-pregnene-20-imino derivatives and process for their preparation |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US3072637A (en) |
| BE (1) | BE586621A (en) |
| DE (1) | DE1131211B (en) |
| FR (1) | FR1284529A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3313698A (en) * | 1962-08-27 | 1967-04-11 | Roussel Uclaf | 20-di-substituted amino-pregnanes |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB491798A (en) * | 1937-03-08 | 1938-09-08 | Ig Farbenindustrie Ag | Manufacture of cyclopentanohydrophenanthrene ketones |
| US2582258A (en) * | 1949-09-17 | 1952-01-15 | Glidden Co | Preparation and degradation of steroid amines |
| US2731461A (en) * | 1952-11-28 | 1956-01-17 | Hoechst Ag | 17-hydroxy compounds of the steroid series |
-
1959
- 1959-12-21 US US860674A patent/US3072637A/en not_active Expired - Lifetime
-
1960
- 1960-01-05 FR FR814832A patent/FR1284529A/en not_active Expired
- 1960-01-07 DE DEC20501A patent/DE1131211B/en active Pending
- 1960-01-15 BE BE586621A patent/BE586621A/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB491798A (en) * | 1937-03-08 | 1938-09-08 | Ig Farbenindustrie Ag | Manufacture of cyclopentanohydrophenanthrene ketones |
| US2582258A (en) * | 1949-09-17 | 1952-01-15 | Glidden Co | Preparation and degradation of steroid amines |
| US2731461A (en) * | 1952-11-28 | 1956-01-17 | Hoechst Ag | 17-hydroxy compounds of the steroid series |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3313698A (en) * | 1962-08-27 | 1967-04-11 | Roussel Uclaf | 20-di-substituted amino-pregnanes |
Also Published As
| Publication number | Publication date |
|---|---|
| DE1131211B (en) | 1962-06-14 |
| BE586621A (en) | 1960-07-13 |
| FR1284529A (en) | 1962-02-16 |
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